ALKYNE FUNCTIONALIZATIONS AS TOOLS FOR HETEROCYCLIC SYNTHESIS

Although the carbon-carbon triple bond is one of the oldest and most versatile functional groups known in organic chemistry, its use in organic synthesis is not as widespread as alkene- or carbonylfunctionalization reactions, at least not until recently. During the last decennium there has been a huge revival of the interest in alkyne functionalization, which is mainly resulting from newly obtained insights in transition-metal catalyzed transformations of alkynes (e.g. catalytic asymmetric Pauson-Khand reactions, catalytic Huisgen cycloaddition 'click'-chemistry, catalyzed alkyne-alkyne coupling, enyne metathesis, etc...). Amongst the variety of used transition-metal catalysts, gold and platinum salts have emerged as powerful tools for activating triple bonds towards nucleophilic attack. Because of the great potential of catalyzed alkyne activation in heterocyclic chemistry, it was decided to evaluate easily available N-propargylamides and related alkynes as substrates for gold-catalyzed cycloisomerization reactions. Substituted N-propargylamides and related urea derivatives proved to be valuable substrates for the rapid synthesis of different oxazoles and imidazolinones, while N-propargyl-3-oxobutanamides and -esters were used to construct furan-fused pyrrolidinones and furanones. Analogously, cycloisomerization of indolyl tethered N-propargylamides gave rise to interesting pyrazinoindolones or oxazoles, depending on the solvent system used. The obtained insights in above described alkyne functionalization reactions were used to synthesize new ?-carbolinones as substrates for biologically relevant heterocycles, such as new analogues of the antibiotic and antitumor compound Lavendamycin. In conclusion, it can be stated that the functionalization of alkynes with nucleophiles, catalyzed by late transition metal catalysts or even by a simple proton, was found to be a good strategy for synthesizing a variety of new azaheterocyclic compounds. General perspectives and new research interests in organic synthesis at the Vrije Universiteit Brussel will be presented.